The indole compound MA-35 attenuates tumorigenesis in an inflammation-induced colon cancer model

Kanehara, Keigo; Ohnuma, Shinobu; Kanazawa, Yoshitake; Sato, Keisuke; Kokubo, Shoji; Suzuki, Hideyuki; Karasawa, Hideaki; Suzuki, Takehiro; Suzuki, Chitose; Naitoh, Takeshi; Unno, Michiaki; Abe, Takaaki

doi:10.1038/s41598-019-48974-9

Cited by 18 publications

(9 citation statements)

References 50 publications

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“…Moreover, hyperplastic tissues and tumors were observed in the intestine of ImiR-21 + Dox ( Figure 6 and Figure S2 ). Similar symptoms were observed in AOM/DSS-treated mouse models [ 63 , 64 ]. Hence, miR-21 has strong oncogenic effects and is critical for CAC and CRC development.…”

Section: Discussionsupporting

confidence: 76%

MicroRNA-21 Plays Multiple Oncometabolic Roles in Colitis-Associated Carcinoma and Colorectal Cancer via the PI3K/AKT, STAT3, and PDCD4/TNF-α Signaling Pathways in Zebrafish

Lai

Yeh

Liu

et al. 2021

Cancers

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Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. Patients with inflammatory bowel disease (IBD) have a high risk of developing CRC. Inflammatory cytokines are regulated by complex gene networks and regulatory RNAs, especially microRNAs. MicroRNA-21 (miR-21) is amongst the most frequently upregulated microRNAs in inflammatory responses and cancer development. miR-21 has become a target for genetic and pharmacological regulation in various diseases. However, the association between inflammation and tumorigenesis in the gut is largely unknown. Hence, in this study, we generated a zebrafish model (ImiR-21) with inducible overexpression of miR-21 in the intestine. The results demonstrate that miR-21 can induce CRC or colitis-associated cancer (CAC) in ImiR-21 through the PI3K/AKT, PDCD4/TNF-α, and IL-6/STAT3 signaling network. miR-21 activated the PI3K/AKT and NF-κB signaling pathways, leading to initial inflammation; thereafter, miR-21 and TNF-α repressed PDCD4 and its tumor suppression activity. Eventually, active STAT3 stimulated a strong inflammatory response and activated the invasion/metastasis process of tumor cells. Hence, our findings indicate that miR-21 is critical for the development of CRC/CAC via the PI3K/AKT, STAT3, and PDCD4/TNF-α signaling networks.

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Section: Discussionsupporting

confidence: 76%

MicroRNA-21 Plays Multiple Oncometabolic Roles in Colitis-Associated Carcinoma and Colorectal Cancer via the PI3K/AKT, STAT3, and PDCD4/TNF-α Signaling Pathways in Zebrafish

Lai

Yeh

Liu

et al. 2021

Cancers

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“…The CAC model mouse was constructed by intra-peritoneal injection of 10 mg/kg AOM and oral 2.0% DSS. 33 , 34 In brief, except the control group, all the animals received intra-peritoneal injection of AOM (10 mg/kg) on the first day. Then, all the groups were treated with the corresponding drug system for 1 week after the AOM injection (set as day1).…”

Section: Methodsmentioning

confidence: 99%

Self-Nanoemulsifying Drug Delivery System of Genkwanin: A Novel Approach for Anti-Colitis-Associated Colorectal Cancer

Yin¹,

Yin²,

Ouyang³

et al. 2021

DDDT

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Purpose The aim of the present study was to develop an optimized Genkwanin (GKA)-loaded self-nanoemulsifying drug delivery system (SNEDDS) formulation to enhance the solubility, intestinal permeability, oral bioavailability and anti-colitis-associated colorectal cancer (CAC) activity of GKA. Methods We designed a SNEDDS comprised oil phase, surfactants and co-surfactants for oral administration of GKA, the best of which were selected by investigating the saturation solubility, constructing pseudo-ternary phase diagrams, followed by optimizing thermodynamic stability, emulsification efficacy, self-nanoemulsification time, droplet size, transmission electron microscopy (TEM), drug release and intestinal permeability. In addition, the physicochemical properties and pharmacokinetics of GKA-SNEDDS were characterized, and its anti-colitis-associated colorectal cancer (CAC) activity and potential mechanisms were evaluated in AOM/DSS-induced C57BL/6J mice model. Results The optimized nanoemulsion formula (OF) consists of Maisine CC, Labrasol ALF and Transcutol HP in a weight ratio of 20:60:20 (w/w/w), in which ratio the OF shows multiple improvements, specifically small mean droplet size, excellent stability, fast release properties as well as enhanced solubility and permeability. Pharmacokinetic studies demonstrated that compared with GKA suspension, the relative bioavailability of GKA-SNEDDS was increased by 353.28%. Moreover, GKA-SNEDDS not only significantly prevents weight loss and improves disease activity index (DAI) but also reduces the histological scores of inflammatory cytokine levels as well as inhibiting the formation of colon tumors via inducing tumor cell apoptosis in the AOM/DSS-induced CAC mice model. Conclusion Our results show that the developed GKA-SNEDDS exhibited enhanced oral bioavailability and excellent anti-CAC efficacy. In summary, GKA-SNEDDS, using lipid nanoparticles as the drug delivery carrier, can be applied as a potential drug delivery system for improving the clinical application of GKA.

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“…Cytokines secreted by the tumor stroma cells lead to an increase in tumor growth and invasiveness by activating oncogenic signaling pathways like nuclear factor kappa B (NF-κB) by tumor necrosis factor-α (TNF-α) and interleukin 1β (IL-1β) and activation of signal transducer and activator of transcription 3 (STAT3) by interleukin 6 (IL-6). − …”

Section: Introductionmentioning

confidence: 99%

Chitosan-Decorated PLGA-NPs Loaded with Tannic Acid/Vitamin E Mitigate Colon Cancer via the NF-κB/β-Cat/EMT Pathway

Nag

Saha

2021

ACS Omega

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Colon cancer is the second highest contributor of cancer-related deaths throughout the world. Treatment strategies with tannic acid and vitamin E are envisaged as desirable and safe owing to their robust antioxidative and anti-inflammatory potential. In the present report, these bioactives have been nanoencapsulated in poly(d,l-lactide-co-glycolic acid) (PLGA) formulations for maintaining sustained release and ensuring enhanced bioavailability. Capping of nanoparticles (NPs) with chitosan was done for enhanced anticancer efficacy and tumor targeting. CS-PLGA-TA-E, administered intraperitoneally, significantly inhibited tumor number and tumor volume and normalized colon histology in the colon cancer. Tissue distribution studies showed that TA/E content from CS-PLGA-TA-E was present in a higher concentration in the tumor tissue than the concentration of TA/E content from PLGA-TA-E or free TA or free E. Also, the TA/E content from all of the treatment groups showed its highest concentration in the tumor compared to other organs. Antioxidant enzymes and proinflammatory cytokines (TNF-α, IL-1β, IL-6) were inhibited by CS-PLGA-TA-E. CS-PLGA-TA-E inhibited markers for tumor growth (EGFR-PI3K-AKT), inflammation (NF-κB/Stat3), β-catenin signaling (β-catenin, c-myc, cyclin D1), EMT (E-cadherin, N-cadherin, vimentin), and apoptosis (Bcl-2) in a significantly greater way as compared with PLGA-TA-E, TA, or E. CS-PLGA-TA-E NPs can be considered promising anticancer drugs for colon cancer.

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The indole compound MA-35 attenuates tumorigenesis in an inflammation-induced colon cancer model

Cited by 18 publications

References 50 publications

MicroRNA-21 Plays Multiple Oncometabolic Roles in Colitis-Associated Carcinoma and Colorectal Cancer via the PI3K/AKT, STAT3, and PDCD4/TNF-α Signaling Pathways in Zebrafish

MicroRNA-21 Plays Multiple Oncometabolic Roles in Colitis-Associated Carcinoma and Colorectal Cancer via the PI3K/AKT, STAT3, and PDCD4/TNF-α Signaling Pathways in Zebrafish

Self-Nanoemulsifying Drug Delivery System of Genkwanin: A Novel Approach for Anti-Colitis-Associated Colorectal Cancer

Chitosan-Decorated PLGA-NPs Loaded with Tannic Acid/Vitamin E Mitigate Colon Cancer via the NF-κB/β-Cat/EMT Pathway

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